Semicarbazone derivatives as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Since long-term use of classic NSAIDs can cause severe side effects related mainly to the gastroduodenal tract, discovery of novel cyclooxygenase inhibitors with a safe gastric profile still remains a crucial challenge. Based on the most recent literature data and previous own studies, we decided to modify the structure of already reported 1,3,4-oxadiazole based derivatives of pyrrolo[3,4-d]pyridazinone in order to obtain effective COX inhibitors. Herein we present the synthesis, biological evaluation and molecular docking studies of 12 novel compounds with disubstituted arylpiperazine pharmacophore linked in a different way with 1,3,4-oxadiazole ring. None of the obtained molecules show cytotoxicity on NHDF and THP-1 cell lines and, therefore, all were qualified for further investigation. In vitro cyclooxygenase inhibition assay revealed almost equal activity of new derivatives towards both COX-1 and COX‑2 isoenzymes. Moreover, all compounds inhibit COX-2 isoform better than Meloxicam which was used as reference. Anti-inflammatory activity was confirmed in biological assays according to which title molecules are able to reduce induced inflammation within cells. Molecular docking studies were performed to describe the binding mode of new structures to cyclooxygenase. Investigated derivatives take place in the active site of COX, very similar to Meloxicam. For some compounds, promising druglikeness was calculated using in silico predictions.

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Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors

ChemistrySelect ◽

10.1002/slct.202000429 ◽

2020 ◽

Vol 5 (18) ◽

pp. 5387-5390

Author(s):

Shams‐Ul Mahmood ◽

Yasir Nazir ◽

Aamer Saeed ◽

Qamar Abbas ◽

Zaman Ashraf

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Urease Inhibitors ◽

Molecular Docking Studies

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Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191105100959 ◽

2019 ◽

Vol 19 (29) ◽

pp. 2676-2686 ◽

Cited By ~ 1

Author(s):

Saddala Madhu Sudhana ◽

Pradeepkiran Jangampalli Adi

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Biological Evaluation ◽

Binding Energies ◽

Molecular Docking Studies ◽

Metal Chelating ◽

In Silico Admet ◽

Dpph Method

Aims: The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Background: An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine) 1 were chemical synthesized process. Materials & Methods: In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds 3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS method), cytotoxicity, molecular docking and in silico ADMET properties. Result: Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but 5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed the best binding energies and non-toxic properties. Conclusion: The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress associated diseases.

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